Meningococcal Conjugate Vaccine Appears Safe in Infants

Emma Hitt, PhD

November 14, 2012

Quadrivalent meningococcal conjugate vaccine (MenACWY-D; Menactra, sanofi pasteur) appears to be safe and immunogenic when given as a 2-dose series in infants at the age of 9 months and 1 year, according to pooled data from 3 randomized trials.

L. Miriam Pina, MD, and colleagues from sanofi pasteur in Swiftwater, Pennsylvania, report their findings in an article published in the November issue of the Pediatric Infectious Disease Journal.

According to the researchers, MenACWY-D was licensed in the United States in 2005 to prevent meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 in teenagers and adults. A second vaccine (MenACWY-CRM; Menveo, Novartis Vaccines and Diagnostics) is also currently indicated for the prevention of invasive meningococcal disease and is approved for children and adults between the ages of 2 and 55 years.

"The license [for MenACWY-D] was extended to children aged 2–10 years in 2007 and extended again in 2011 to infants aged 9 months and older based, in part, on results from 3 phase III studies presented herein," the authors note.

To further evaluate the safety, data from these 3 trials conducted between September 2006 and January 2009 were assessed. One study enrolled 1257 participants, another study enrolled 2289 participants, and a third study enrolled 1378 participants.

At 30 days after vaccination, immunogenicity, as measured by assays of human complement titer levels (titers ≥1:8), was demonstrated in between 86.4% and 100% of children receiving 2 doses of the vaccine at ages 9 and 12 months. A titer ≥1:4 to each serogroup was achieved by more than 91% of vaccinated children.

In addition, the vaccine did not appear to interfere with the measles, mumps, rubella, and varicella or heptavalent pneumococcal conjugate vaccines, with between 81% and 98% of participants receiving concomitant vaccinations achieving protective responses.

Antipneumococcal antibody levels were decreased when the meningococcal vaccine was given with the heptavalent pneumococcal conjugate vaccine but remained protective for all serotypes by enzyme-linked immunosorbent assay (98% - 100%, ≥0.35 μg/mL) and opsonophagocytic assay (99% - 100%, ≥1:8).

According to the authors, adverse events were generally mild and similar across groups. "Injection-site and systemic events were similar to those of currently licensed, routinely administered pediatric vaccines," they add. Of the participants, between 23.3% and 30.1% reported erythema and between 10.1% and 16.2% reported swelling. Most injection-site reactions were reported within 3 days of the vaccination and were mild and transient.

Serious adverse events were reported in between 3% and 5% of participants receiving MenACWY-D, but they were also reported in 2% and 4% of control patients. In the 3 studies combined, 4 serious adverse events were considered related to the study vaccine: insulin-dependent diabetes mellitus, respiratory distress, and 2 cases of febrile seizures.

"In summary, MenACWY-D offers the broad protection of a quadrivalent vaccine among children 9–23 months of age when administered as a 2-dose schedule, 3 months apart," Dr. Pina and colleagues conclude. "This schedule can protect infants with fewer doses than a classic 3+1 infant schedule, and it minimizes the risk of interference and the difficulties associated with the introduction of another vaccine into an already crowded infant vaccination schedule."

Independent commentator Doug Campos-Outcalt, MD, from the University of Arizona College of Medicine in Phoenix, told Medscape Medical News that the findings support previous data showing the safety with this vaccine, but the "numbers in the study are not enough to detect rare serious adverse events."

Dr. Campos-Outcalt pointed out that it remains to be determined whether there are rare serious adverse events, noting that "when the target disease is so rare, the issue of safety becomes paramount."

"At the moment, meningococcal vaccines are recommended only for high-risk infants," he added.

This research was funded by sanofi pasteur Inc, which employs and authors. Dr. Campos-Outcalt has disclosed no relevant financial relationships.

Pediatr Infect Dis J. 2012;31:1173-1183. Full text